Subanesthetic doses of phencylclidine increase the turnover rate of acetylcholine in frontal and parietal cortex, but not in striatum or hippocampus when animals are sacrificed 30 minutes after drug treatment. Phencyclidine-induced increase in cortical acetylcholine turnover rate was temporally correlated with the behavior effects of this compound. These results suggest that an activation of cortical cholinergic neurons may be related to these behavioral effects. In contrast to recent reports of specific 3H-phenyclidine binding sites in rat brain, we demonstrated that this binding is actually an artifact of the rapid filtration assay. 3H-phencyclidine binds to the glass fiber filters used in this assay in a manner resembling specific binding.